The recent event involving the off-label use of avastin (bivacizumab injection, 100 mg/4mL) should serve as an eye-opener to pediatricians. In an unfortunate incident, a few patients lost vision after an ophthalmological procedure [1]. The regulator, Central Drugs Standard Control Organization (CDSCO) chose to issue a warning pointing out that avastin used in these patients is not approved for use in ophthalmology, and directed that such use be desisted from [1]. The warning was later withdrawn [2], once it was noted that although off-label, its use as an anti-vascular endothelial growth factor (VEGF) for the treatment of age-related macular degeneration (AMD) is endorsed by the WHO [3], International Council of Ophthalmology, National Institutes of Health, and regulatory agencies of France and Italy [2]. However, the event brought the issue of off-label drugs into a sharp focus.

Off-label drug-use is a reality and needs to be resorted to, as the discoveries made after market authorization compel medical practitioners to use the drug for new indications, in new populations using better dosage regimens. As children are usually not enrolled in clinical trials, many drugs continue to be marketed without appropriate pediatric labeling. Pediatricians prescribe drugs on the basis of available evidence (as they should), textbook-material, guidelines or consensus statements. This ensures that children are treated with better therapies as per new evidence. But, if it is used for indications not listed in the license or is administered in a manner (dose, dose regimen, route of administration, etc.) not described in the license; the use constitutes off-label drug use. Off-label drug use is highly prevalent in neonates and children [4,5], and while prescribing these drugs, the treating pediatricians have a greater responsibility. If any controversy arises, they are required to prove that they acted in good faith and that their actions are supported by available evidence.

As the parents and media may misconstrue off-label use as experimental or unapproved use, the pediatrician can face rough weather. In addition, the accelerated reaction of the regulator might put an additional stress. It is imperative that the Indian Academy of Pediatrics (IAP) comes out with a guidance statement for its members regarding off-label use of drugs, detailing the legal position, role of the regulator, therapeutic decision- making process and prescriber responsibilities. As off-label use is highly prevalent among pregnant women, cancer patients and psychiatric patients as well; the Academy should collaborate with professional organizations of these specialties to plead with the regulator and policy makers for facilitating change in labels in case of older drugs, where a considerable body of evidence is available. This will help assure parents, media and the society at large that the drug therapy is safe and efficacious. IAP should also come out with evidence-based updated guidelines for management of pediatric conditions. This will act as support and a ready-reference when a pediatrician is required to employ off-label drug.

1. Directorate General of Health Services. Office of the Drugs Controller General of India (DCGI). Notice. F No. 12-52/2004-DC (Part I). Available from: http://www.dfda.goa.gov.in/images/uploads/ale_not.pdf. Accessed May 16, 2016.

2. Directorate General of Health Services. Office of the Drugs Controller General of India (DCGI). Notice. F No. 12-52/2004-DC (Part I). Available from: http://www.cdsco.nic.in/writereaddata/ AVASTIN.pdf. Accessed May 15, 2016.

3. World Health Organization. WHO Model List of Essential Medicines. 19th list (April 2015) (Amended June 2015). Available from: http://www.who.int/selection_medicines/committees/expert/20/EML_2015_FINAL_amended_ JUN2015.pdf?ua=1. Accessed May 15, 2016.

4. Jain S, Saini SS, Chawla D, Kumar P, Dhir S. Off-label use of drugs in neonatal intensive care units. Indian Pediatr. 2014;51:644-6.